Existence and uniqueness theorems for massless fields on a class of spacetimes with closed timelike curves

We study the massless scalar field on asymptotically flat spacetimes with closed timelike curves (CTC's), in which all future-directed CTC's traverse one end of a handle (wormhole) and emerge from the other end at an earlier time. For a class of static geometries of this type, and for smooth initial data with all derivatives in $L_2$ on {\cI}^{-}, we prove existence of smooth solutions which are regular at null and spatial infinity (have finite energy and finite $L_2$-norm) and have the given initial data on \cI^-. A restricted uniqueness theorem is obtained, applying to solutions that fall off in time at any fixed spatial position. For a complementary class of spacetimes in which CTC's are confined to a compact region, we show that when solutions exist they are unique in regions exterior to the CTC's. (We believe that more stringent uniqueness theorems hold, and that the present limitations are our own.) An extension of these results to Maxwell fields and massless spinor fields is sketched. Finally, we discuss a conjecture that the Cauchy problem for free fields is well defined in the presence of CTC's whenever the problem is well-posed in the geometric-optics limit. We provide some evidence in support of this conjecture, and we present counterexamples that show that neither existence nor uniqueness is guaranteed under weaker conditions. In particular, both existence and uniqueness can fail in smooth, asymptotically flat spacetimes with a compact nonchronal region.Comment: 47 pages, Revtex, 7 figures (available upon request

Structure and Response in the World Trade Network

We examine how the structure of the world trade network has been shaped by globalization and recessions over the last 40 years. We show that by treating the world trade network as an evolving system, theory predicts the trade network is more sensitive to evolutionary shocks and recovers more slowly from them now than it did 40 years ago, due to structural changes in the world trade network induced by globalization. We also show that recession-induced change to the world trade network leads to an \emph{increased} hierarchical structure of the global trade network for a few years after the recession.Comment: 4 pages, 4 figures, to appear in Phys. Rev. Let

Time series gene expression profiling and temporal regulatory pathway analysis of BMP6 induced osteoblast differentiation and mineralization

Background: BMP6 mediated osteoblast differentiation plays a key role in skeletal development and bone disease. Unfortunately, the signaling pathways regulated by BMP6 are largely uncharacterized due to both a lack of data and the complexity of the response. Results: To better characterize the signaling pathways responsive to BMP6, we conducted a time series microarray study to track BMP6 induced osteoblast differentiation and mineralization. These temporal data were analyzed using a customized gene set analysis approach to identify temporally coherent sets of genes that act downstream of BMP6. Our analysis identified BMP6 regulation of previously reported pathways, such as the TGF-beta pathway. We also identified previously unknown connections between BMP6 and pathways such as Notch signaling and the MYB and BAF57 regulatory modules. In addition, we identify a super-network of pathways that are sequentially activated following BMP6 induction. Conclusion: In this work, we carried out a microarray-based temporal regulatory pathway analysis of BMP6 induced osteoblast differentiation and mineralization using GAGE method. This novel temporal analysis is more informative and powerful than the classical static pathway analysis in that: (1) it captures the interconnections between signaling pathways or functional modules and demonstrates the even higher level organization of molecular biological systems; (2) it describes the temporal perturbation patterns of each pathway or module and their dynamic roles in osteoblast differentiation. The same set of experimental and computational strategies employed in our work could be useful for studying other complex biological processes

The Neighborhood’s Catalogue: Lower East Side Planning and Design File

This catalogue was designed to support the process of slow redevelopment over time, combined with conservation of diverse social and historical continuity and the exploration of new land and building uses. The catalogue shows how to involve neighborhoods in participation, supportive design, incremental planning and phased development. This project was made possible by a grant from the National Endowment for the Arts. Reprinted in 1987.https://dc.uwm.edu/caupr_mono/1047/thumbnail.jp

The Foundation of and Future Directions for JEDI @ University of Massachusetts Amherst Libraries

This chapter per the authors provides an in-depth overview of how the University of Massachusetts Amherst Libraries has leveraged historical connections and special collections to provide a robust foundation for justice, equity, diversity, and inclusion programming and initiatives on campus, in the community, and worldwide. Readers will be provided with examples that will inform conversations about JEDI efforts at their own libraries and on their own campuses, as well as insights gleaned during the process of doing this work at University of Massachusetts Amherst Libraries

GAGE: generally applicable gene set enrichment for pathway analysis

<p>Abstract</p> <p>Background</p> <p>Gene set analysis (GSA) is a widely used strategy for gene expression data analysis based on pathway knowledge. GSA focuses on sets of related genes and has established major advantages over individual gene analyses, including greater robustness, sensitivity and biological relevance. However, previous GSA methods have limited usage as they cannot handle datasets of different sample sizes or experimental designs.</p> <p>Results</p> <p>To address these limitations, we present a new GSA method called Generally Applicable Gene-set Enrichment (GAGE). We successfully apply GAGE to multiple microarray datasets with different sample sizes, experimental designs and profiling techniques. GAGE shows significantly better results when compared to two other commonly used GSA methods of GSEA and PAGE. We demonstrate this improvement in the following three aspects: (1) consistency across repeated studies/experiments; (2) sensitivity and specificity; (3) biological relevance of the regulatory mechanisms inferred.</p> <p>GAGE reveals novel and relevant regulatory mechanisms from both published and previously unpublished microarray studies. From two published lung cancer data sets, GAGE derived a more cohesive and predictive mechanistic scheme underlying lung cancer progress and metastasis. For a previously unpublished BMP6 study, GAGE predicted novel regulatory mechanisms for BMP6 induced osteoblast differentiation, including the canonical BMP-TGF beta signaling, JAK-STAT signaling, Wnt signaling, and estrogen signaling pathways–all of which are supported by the experimental literature.</p> <p>Conclusion</p> <p>GAGE is generally applicable to gene expression datasets with different sample sizes and experimental designs. GAGE consistently outperformed two most frequently used GSA methods and inferred statistically and biologically more relevant regulatory pathways. The GAGE method is implemented in R in the "gage" package, available under the GNU GPL from <url>http://sysbio.engin.umich.edu/~luow/downloads.php</url>.</p

Highly efficient genetic transduction of primary human synoviocytes with concentrated retroviral supernatant

Abstract We are developing retroviral-mediated gene transfer to human fibroblast-like synovial cells (FLS) as one approach to characterizing genetic pathways involved in synoviocyte pathophysiology. Prior work has suggested that FLS are relatively refractory to infection by Moloney murine leukemia virus based vectors. To determine if viral titer influenced the transduction efficiency of FLS, we optimized a rapid, efficient, and inexpensive centrifugation method to concentrate recombinant retroviral supernatant. The technique was evaluated by measurement of the expression of a viral enhanced green fluorescent protein transgene in transduced cells, and by analysis of viral RNA in retroviral supernatant. Concentration (100-fold) was achieved by centrifugation of viral supernatant for four hours, with 100% recovery of viral particles. The transduction of FLS increased from approximately 15% with unconcentrated supernatant, to nearly 50% using concentrated supernatant. This protocol will be useful for investigators with applications that require efficient, stable, high level transgene expression in primary FLS.http://deepblue.lib.umich.edu/bitstream/2027.42/109454/1/13075_2000_Article_409.pd